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Association of common genetic variation in the insulin/IGF1 signaling pathway with human longevity.
Tuesday,2012-11-06 12:18 America/Los_Angeles — eenright
| Title | Association of common genetic variation in the insulin/IGF1 signaling pathway with human longevity. |
| Publication Type | Journal Article |
| Year of Publication | 2009 |
| Authors | Pawlikowska, L, Hu, D, Huntsman, S, Sung, A, Chu, C, Chen, J, Joyner, AH, Schork, NJ, Hsueh, W-C, Reiner, AP, Psaty, BM, Atzmon, G, Barzilai, N, Cummings, SR, Browner, WS, Kwok, P-Y, Ziv, E |
| Corporate/Institutional Authors | Study of Osteoporotic Fractures, |
| Journal | Aging Cell |
| Volume | 8 |
| Issue | 4 |
| Pagination | 460-72 |
| Date Published | 2009 Aug |
| ISSN | 1474-9726 |
| Keywords | Aged, Aged, 80 and over, Female, Follow-Up Studies, Forkhead Box Protein O3, Forkhead Transcription Factors, Genome, Human, Genotype, Humans, Insulin, Insulin-Like Growth Factor I, Longevity, Male, Osteoporosis, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins c-akt, Signal Transduction |
| Abstract | <p>The insulin/IGF1 signaling pathways affect lifespan in several model organisms, including worms, flies and mice. To investigate whether common genetic variation in this pathway influences lifespan in humans, we genotyped 291 common variants in 30 genes encoding proteins in the insulin/IGF1 signaling pathway in a cohort of elderly Caucasian women selected from the Study of Osteoporotic Fractures (SOF). The cohort included 293 long-lived cases (lifespan > or = 92 years (y), mean +/- standard deviation (SD) = 95.3 +/- 2.2y) and 603 average-lifespan controls (lifespan < or = 79y, mean = 75.7 +/- 2.6y). Variants were selected for genotyping using a haplotype-tagging approach. We found a modest excess of variants nominally associated with longevity. Nominally significant variants were then replicated in two additional Caucasian cohorts including both males and females: the Cardiovascular Health Study and Ashkenazi Jewish Centenarians. An intronic single nucleotide polymorphism in AKT1, rs3803304, was significantly associated with lifespan in a meta-analysis across the three cohorts (OR = 0.78 95%CI = 0.68-0.89, adjusted P = 0.043); two intronic single nucleotide polymorphisms in FOXO3A demonstrated a significant lifespan association among women only (rs1935949, OR = 1.35, 95%CI = 1.15-1.57, adjusted P = 0.0093). These results demonstrate that common variants in several genes in the insulin/IGF1 pathway are associated with human lifespan.</p> |
| DOI | 10.1111/j.1474-9726.2009.00493.x |
| Alternate Journal | Aging Cell |
| PubMed ID | 19489743 |
| PubMed Central ID | PMC3652804 |
| Grant List | 5U19AG023122 / AG / NIA NIH HHS / United States N01-HC-85085 / HC / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States 2 R01 AG005394-22A1 / AG / NIA NIH HHS / United States U19 AG023122 / AG / NIA NIH HHS / United States AG05407 / AG / NIA NIH HHS / United States N01-HC-85081 / HC / NHLBI NIH HHS / United States R01 AR035583 / AR / NIAMS NIH HHS / United States AR35582 / AR / NIAMS NIH HHS / United States HHSN268200800007C / HL / NHLBI NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States R01 AR035584 / AR / NIAMS NIH HHS / United States AG05394 / AG / NIA NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States R01 AG027576 / AG / NIA NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States 2 R01 AG027574-22A1 / AG / NIA NIH HHS / United States U19 AG023122-05 / AG / NIA NIH HHS / United States N01-HC-85082 / HC / NHLBI NIH HHS / United States N01 HC-55222 / HC / NHLBI NIH HHS / United States R01 AG005407 / AG / NIA NIH HHS / United States R01 AG027576-22 / AG / NIA NIH HHS / United States AR35583 / AR / NIAMS NIH HHS / United States N01-HC-85083 / HC / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States N01-HC-85080 / HC / NHLBI NIH HHS / United States T32 GM007752 / GM / NIGMS NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States R01 AR035582 / AR / NIAMS NIH HHS / United States R01 AG005394 / AG / NIA NIH HHS / United States AR35584 / AR / NIAMS NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States R01 AG027574 / AG / NIA NIH HHS / United States N01-HC-85084 / HC / NHLBI NIH HHS / United States |